Maternal tolerance of the fetal allograft remains poorly understood. In humans, expres-sion of the highly polymorphic classical HLA-A and HLA-B loci is suppressed, while expression of the nonclassical HLA-G locus is up-regulated at the maternal-fetal interface. Like other nonclassical MHC class I molecules, HLA-G exhibits limited diversity, but certain characteristics of HLA-G distin-guish it from other nonclassical MHC class I molecules it has a truncated cytoplasmic domain, it is the product of alternatively spliced mRNAs, and it is expressed primarily in the placenta. We have ex-amined MHC class I expression in the placenta of the rhesus monkey to determine whether this ani-mal is a suitable model in which to study the function of HLA-G. Although this species possesses or-thologs of many MHC class I and II loci found in humans, the HLA-G ortholog is a pseudogene in the rhesus monkey. In this study, we report the identification of a novel nonclassical MHC class I locus expressed in the placenta of the rhesus monkey, Mamu-AG (Macaca mulatta-AG). Although unrelated to HLA-G, Mamu-AG encodes glycoproteins with all of the characteristics of HLA-G. These Mamu-AG glycoproteins are limited in their diversity, possess truncated cytoplasmic domains, are the products of alternatively spliced mRNAs, and their expression is restricted to the placenta. OBJECTIVE: To determine MHC class I genes expressed in the rhesus monkey placenta. RESULTS Taken together, these data suggest that convergent evolution may have resulted in the expression of a unique nonclassical MHC class I molecule in the rhesus monkey placenta, and that the common structural features of Mamu-AG and HLA-G may be functionally significant. FUTURE DIRECTIONS This funding supports the use of the rhesus as an animal model for studying the interaction between the maternal immune system and the fetus in humans. KEY WORDS HLA-G, placenta, MHC, Rhesus